The drugs with low bioavailability, when orally administered, do not work even though they are intrinsically endowed with good efficacy. For this reason, many efforts have been made to enhance the bioavailability of the drugs, particularly small intestinal or nasal mucous membrane permeability when the drugs are administered by oral or nasal route.
Boosting the mucous membrane permeation of drugs with a permeation enhancer can be taken into consideration, where the permeation enhancer promotes the transfer of drugs passing through the paracellular route, that is, the intercellular space between the mucous membrane cells. Examples of the permeation enhancer include surfactants, or peptides or proteins that affect the tight junctions. Yet, the surfactants are toxic to the cells, and the peptides or proteins are likely to display low physicochemical stability depending on the pH value of the administered drugs or the absorbing areas due to their structural properties. The use of the surfactants is thus very limited. The peptides or proteins that affect the tight junctions are almost nontoxic to the cells, yet they are required to go with adjuvants or additives like carrageenan, remaining the problem in association with the preparation and reactivity with the administered drugs.
It is therefore necessary to develop a method and substance as a permeation enhancer that is nontoxic to the cells and capable of affecting the open/close of the tight junctions and enhancing the permeation of drugs without the aid of an adjuvant or an additive.